6 HemeNon-erythroidErythroidHaemoglobinHaemoproteinsElectron transfer and energy trappingmyoglobinCytochromesOthers
7 Porphyrins synthesisMitochondrionCytosolSpontaneousURO ICOPRO I
8 ALA synthase + Water-soluble D-ALA Excreted in urine ALA dehydrase GlycineALA synthase+NH2-CH2-COOHWater-solubleExcreted in urineD-ALAALA dehydrasePBG deaminaseWater-solubleExcreted in urinePBGHydroxymethylbilane
9 HydroxymethylbilaneURO III synthaseSpontaneousURO ICOPRO IURO IIIdecarboxylaseUroporphyrinogen IIIWater-solubleExcreted in urineLess water-solubleExcreted in urine/fecesCoproporphyrinogen III
10 CORPO IIICOPRO oxidaseProtoporphyrinogen IXPoor water-solubilityExcreted in fecesPROTO oxidaseProtoporphyrin IXFerrochelataseHeme
22 Sunnybrook Health Sciences Center Sampling Guide Hepatic Porphyrias (normal RBC Porphyrins)Erythropoietic Porphyrias ( RBC Porphyrins)Acute Intermittent Porphyria (AIP)Congenital Erythropoietic Porphyria (CEP)Variegate porphyria (VP)Erythropoietic Protoporphyria (EP)Hereditary Coproporphyria (HCP)Porphyria Cutanea Tarda (PCT)Presentation:PorphyriasTests to orderSampleAcute symptomsAIP1. Urine Porphyrin Precursors Screen & QuantitationRandom (50 ml) or 24-h with Tartaric acidAcute symptoms + skin lesions (may occur independently)VPHCP2. Feces Porphyrins Screen & QuantitationRandomSkin lesionsPCTCEPEP3. Urine Porphyrins Screen & Quantitation4. RBC Porphyrins Screen & QuantitationRandom (50 ml) or 24-h with Na2CO3Lavender-top (EDTA) blood; need HctNotes:At time of acute attack:1. Collect a random urine sample first (50 ml with no preservatives), before attempting to collect a 24-h sample.2. Request "Porphyrin Precursors" (ALA & PBG) instead of "Porphyrins" screen and quantitation. The Laboratory will have to adjust pH to 4-6 for "Porphyrin Precursors", but pH 8-10 for "Porphyrins". - The commonest problem causing confusion!3. All sample containers should be covered with tin foil to shield off from light.
26 CASEA boy, average hematologic parameters over the subsequent 3 years were as follows:Mean corpuscular volume (MCV), 67 fL →microcyticIron studies were unremarkable →Defect in:Porphyrin synthesisHeme synthesisGlobin synthesisHemoglobin (Hb) level, 70.0 g/L;Mean corpuscular hemoglobin level, consistently < 20 pg;Reticulocyte counts ranged from 3.6% to 6.7%;
27 A physical examination revealed scars on the face, hands, and forearms photosensitive bullous dermatosisThe diapers exhibited brilliant pink fluorescence when illuminated with long-range ultraviolet light. → Photosensitive porphyrin ringsFluorescent red cells were detected using a microscope fitted with a 405 nm light source. → CEP or EPA 50-mL urine sample contained 2003 ug uroporphyrin (normal, trace); 92% of this was uro-I. → CEPErythrocyte UROS activity was 21% of the normal mean. Collectively, these findings confirmed the diagnosis of CEP.
28 Erythrocyte UROS activity was normal in both parents, an unexpected finding as obligate carriers (heterozygotes) for UROS mutations generally have half-normal enzymatic activity.UROS was sequenced, and no mutations or deletions were found in thechild or the parents.A GATA1 point mutation was found in the child at codon 216, changing arginine to tryptophan (R216W), as well as on 1 of the 2 GATA1 alleles of his mother and maternal grandmother.GATA1 gene, at Xp11.23, encodes a transcription factor, GATA bindingfactor 1 (GATA-1), that is critical for normal erythropoiesis, globingene expression, and megakaryocyte development.GATA-1 also regulates expression of UROS in developing erythrocytes.
29 General Symptomology: __Abdominal pain ___Abdominal tenderness ___Loss of appetite ___Nausea ___Vomiting ___Constipation ___Carbohydrate craving ___Breast secretions ___Diarrhea ___Partial ileus [Intestinal blockage] ___Abdominal distention ___Dysuria [Painful Urination] ___Bladder Dysfunction ___Urinary Retention ___Amenorrhea [Lack of menses] Physical Findings of Acute Attack __Red or dark urine ___Tachycardia [Pulse] >100 ___Labile hypertension >90 diastolic [blood pressure] ___Fever [Pyrexia] ___Profused sweating ___Edema [Retention of fluids] [Swelling] ___Postural Hypotension [Low Blood Pressure] ___Hypertrichosis [excessive body hair growth] ___Hyperpigmentation [skin coloring]